Shelest B. Endothelial dysfunction and inflammatory markers of chronic kidney disease associated with essential hypertension and its correction.

Dissertation is devoted to improving of diagnosis and treatment of the patients with chronic kidney disease (CKD) associated with essential hypertension (EH) by studying the role of endothelial dysfunction, inflammatory mechanisms during progressing of CKD and EH, by examining the changes mentioned markers under the influence of therapy by Angiotensin Converting Enzyme inhibitor (ACEi) lisinoprilum or Angiotensin Receptor Blockers (ARB) kandesartan. We observed 107 patients. There were 43 patients in first group with CKD associated with EH, 31 patients composed the second group with isolated CKD and there were 33 patients with EH in 3rd group. All patients were investigated by usual clinical routine methods, biochemical methods, ECG, ultrasound investigation of heart, reactive hyperemia, by ELISA there were estimated Willebrand factor (Wf), S-nitrosothiols, IL-4, IL-1?, TNF-?, C-RP. It was established that patients with isolated CKD had endothelial dysfunction and this disorder grew according to the progressing of kidney pathology. The most significant violations were diagnosed in patients with CKD associated with EH. These disorders were proved by dynamics of Willebrand factor. The lowest level of S-nitrosothiols was in patients with CKD comorbid with EH - 0,112 mmol/l, and it was twice lower than from control group. Revealed that the leading pathogenetic mechanism of endothelial dysfunction is decreasing in plasma levels of nitric oxide, which is indicated by its stable metabolites-S-nitrosothiols. Proved that activation of inflammatory mechanisms with increasing of C-RP and anti-inflammatory cytokines TNF-?, IL-1? and decreasing anti-inflammatory IL-4 depends on the severity of CKD and hypertension severity. The intensivity of inflammation in CKD with hypertension progresses with the disease. Activation of TNF-? and IL-1? reached a maximum in CKD stages associated with hypertension, anti-inflammatory IL-4 was reduced in all examined forms of the disease. Іt was demonstrated the effectiveness of ACE inhibitors - lisinopril and ARB II candesartan in patients with CKD with EH not only as antihypertensive drugs, but also their endothelial protect effects and those that influence on the inflammatory processes in this cohort of patients. Endothelial protective and anti-inflammatory effects had developed after 2-3 weeks of treatment. As a result of 2-month observation revealed that lisinopril and candesartan have nephroprotective qualities and may be used as the drug of choice in the treatment of CKD associated with essential hypertension.